The RBBP6/ZBTB38/MCM10 Axis Regulates DNA Replication and Common Fragile Site Stability

Miotto, Benoît; Chibi, Moredreck; Xie, Ping; Koundrioukoff, Stéphane; Moolman-Smook, Hanlie; Pugh, D.J.R.; Debatisse, Michèlle; He, Fei; Zhang, Lingqiang; Defossez, Pierre‐Antoine

doi:10.1016/j.celrep.2014.03.030

Cited by 67 publications

(85 citation statements)

References 54 publications

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“…Multiple independent studies have identified Mcm10 as a major protector of genome integrity [1], [2], especially at common fragile sites [3]. Mcm10 binds to replication origins at the end of G1 phase after the Mcm2-7 core helicase has been loaded onto chromatin as an inactive double-hexamer [4], [5], [6].…”

Section: Introductionmentioning

confidence: 99%

Mapping ubiquitination sites of S. cerevisiae Mcm10

Zhang¹,

Fultz²,

Das-Bradoo³

et al. 2016

Biochemistry and Biophysics Reports

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Minichromosome maintenance protein (Mcm) 10 is a part of the eukaryotic replication machinery and highly conserved throughout evolution. As a multivalent DNA scaffold, Mcm10 coordinates the action of proteins that are indispensable for lagging strand synthesis, such as the replication clamp, proliferating cell nuclear antigen (PCNA). The binding between Mcm10 and PCNA serves an essential function during DNA elongation and is mediated by the ubiquitination of Mcm10. Here we map lysine 372 as the primary attachment site for ubiquitin on S. cerevisiae Mcm10. Moreover, we identify five additional lysines that can be ubiquitinated. Mutation of lysine 372 to arginine ablates ubiquitination of overexpressed protein and causes sensitivity to the replication inhibitor hydroxyurea in cells that are S-phase checkpoint compromised. Together, these findings reveal the high selectivity of the ubiquitination machinery that targets Mcm10 and that ubiquitination has a role in suppressing replication stress.

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Section: Introductionmentioning

confidence: 99%

Mapping ubiquitination sites of S. cerevisiae Mcm10

Zhang¹,

Fultz²,

Das-Bradoo³

et al. 2016

Biochemistry and Biophysics Reports

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“…For example, Mpe1 has been implicated in regulating ubiquitination of PAP and potentially other factors (Lee and Moore 2014). Rbbp6 has also been shown to possess E3 ligase activity and function as an activator of Mdm2-mediated ubiquitination of p53 (Li et al 2007;Miotto et al 2014). Finally, a splice isoform of Rbbp6, called iso3 and consisting solely of the DWNN, competes with the full-length protein to modulate cleavage efficiency (Di Giammartino et al 2014).…”

Section: Rbbp6 and Pas Recognitionmentioning

confidence: 99%

The end of the message: multiple protein–RNA interactions define the mRNA polyadenylation site

2015

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The key RNA sequence elements and protein factors necessary for 3 ′ processing of polyadenylated mRNA precursors are well known. Recent studies, however, have significantly reshaped current models for the protein-RNA interactions involved in poly(A) site recognition, painting a picture more complex than previously envisioned and also providing new insights into regulation of this important step in gene expression. Here we review the recent advances in this area and provide a perspective for future studies.

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“…The RING domain of RBBP6 binds to YB-1, a multifunctional RNA-binding protein, and the transcriptional repressor ZBTB38. Both proteins were shown to be substrates of RBBP6 for ubiquitination, leading to their degradation by the proteasome (Chibi et al 2008;Miotto et al 2014). Mammalian RBBP6 also includes a long C-terminal extension containing several additional significant domains.…”

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confidence: 99%

RBBP6 isoforms regulate the human polyadenylation machinery and modulate expression of mRNAs with AU-rich 3′ UTRs

Giammartino

Ogami

et al. 2014

Genes Dev.

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Polyadenylation of mRNA precursors is mediated by a large multisubunit protein complex. Here we show that RBBP6 (retinoblastoma-binding protein 6), identified initially as an Rb-and p53-binding protein, is a component of this complex and functions in 39 processing in vitro and in vivo. RBBP6 associates with other core factors, and this interaction is mediated by an unusual ubiquitin-like domain, DWNN (''domain with no name''), that is required for 39 processing activity. The DWNN is also expressed, via alternative RNA processing, as a small single-domain protein (isoform 3 [iso3]). Importantly, we show that iso3, known to be down-regulated in several cancers, competes with RBBP6 for binding to the core machinery, thereby inhibiting 39 processing. Genome-wide analyses following RBBP6 knockdown revealed decreased transcript levels, especially of mRNAs with AU-rich 39 untranslated regions (UTRs) such as c-Fos and c-Jun, and increased usage of distal poly(A) sites. Our results implicate RBBP6 and iso3 as novel regulators of 39 processing, especially of RNAs with AU-rich 39 UTRs.

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The RBBP6/ZBTB38/MCM10 Axis Regulates DNA Replication and Common Fragile Site Stability

Cited by 67 publications

References 54 publications

Mapping ubiquitination sites of S. cerevisiae Mcm10

Mapping ubiquitination sites of S. cerevisiae Mcm10

The end of the message: multiple protein–RNA interactions define the mRNA polyadenylation site

RBBP6 isoforms regulate the human polyadenylation machinery and modulate expression of mRNAs with AU-rich 3′ UTRs

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